tbuckley/cabot-search huggingface dataset:
Abstract 9737: Association of Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Post-menopausal Women: The Multi-Ethnic Study of Atherosclerosis
Authors: Omar Chehab, Mahsima Shabani, Vinithra Varadarajan, Collin Wu, Karol E Watson, Joseph Yeboah, Wendy S Post, Bharath Ambale-Venkatesh, David A Bluemke, Erin D Michos, Joao A Ac Lima
Journal: Circulation (2022)

Introduction: Endogenous sex hormone(ESH) imbalances have been linked to a higher risk of heart failure in men and post-menopausal women(PMW). However, experimental studies have found conflicting results regarding ESH' response to myocardial fibrosis(MF). Hypothesis: We hypothesize that at baseline, men and PMW with abnormal ESH profiles will have higher rates of MF measured by CMR T1 mapping and higher rates of myocardial scar detected by CMR during a ten-year follow up. Methods: A total of 1,276 men and 1,048 PMW were included in the MESA with ESH measured at baseline and had undergone CMR 10 years later. All analyses were stratified by sex and age groups (Table1A-B). Multivariable linear regression models were constructed to assess the associations of baseline ESH, ECV, and nativeT1 time. Multivariable logistic regression models were built to determine the associations of baseline ESH and myocardial scar among men. Results: Each 1-SD increment higher free and bioavailable testosterone in older men (≥65) was associated with 2.5% (p=0.008) and 1.0%(p=0.08) lower ECV, respectively, and 21.5%(p=0.03) and13.4%lower native T1(p=0.02). A 1-SD increment greater SHBG level was associated with 2%(p=0.01) higher ECV and 12% higher native T1 (p=0.08)(Table1A). Among post-menopausal women of 44-54 years, a 1-SD increment higher free testosterone was associated with 14% greater native T1 only; however, those between 55-64 years, a 1-SD increment higher total testosterone was associated with 9% lower native T1 (Table1B). Higher levels of estradiol in older men (≥65 years) were independently associated with a significantly higher odds of having a myocardial scar (OR:4.10,95%CI:1.35-12.40;p=0.01). Conclusions: Among older men, lower free testosterone and higher levels of estradiol were independently associated with CMR-defined interstitial MF and replacement fibrosis, respectively. There was no consistent association between ESH and interstitial MF among PMW.
Abstract 9623: Shared Decision Making for Atrial Fibrillation: An Overview of Seven Studies Within an Encounter - Randomized Trial
Authors: Marleen Kunneman, Megan Branda, Ian Hargraves, Angela Sivly, Alexander Lee, Haeshik Gorr, Bruce Burnett, Takeki Suzuki, Elizabeth A Jackson, Erik Hess, Mark Linzer, Sarah McCarthy, Celia Kamath, Juan Brito, Peter A Noseworthy, Victor M Montori
Journal: Circulation (2022)

Introduction: Shared decision-making (SDM) about anticoagulant treatment in patients with atrial fibrillation (AF) is widely recommended but its effectiveness is unclear. We assessed the extent to which using an SDM tool promotes high-quality SDM. Hypothesis: SDM will improve communication quality, knowledge, and decisional conflict and will translate to improved medication adherence and outcomes. Methods: In this multicentre encounter-randomized trial, we included patients with nonvalvular AF considering starting/reviewing anticoagulation, and their clinicians. We compared usual care with or without ANTICOAGULATION CHOICE, an SDM conversation tool for use during the clinical encounter that presents individualized risk estimates and compares anticoagulation options across patient important issues. Results: We enrolled and video-recorded 922 patient-clinician encounters. So far, our data have shown that participants in both arms reported near-optimal communication quality, knowledge, and decisional conflict (JAMA IM-2020). Patients in intervention-arm estimated their stroke risks more accurately and were more involved in decision-making (JAMA IM-2020), clinicians were more satisfied (JAMA IM-2020), and cost conversation were more common (JAMA NO-2021). Use of the intervention had no effect on treatment decisions, encounter duration (JAMA IM-2020), treatment adherence, clinical outcomes (JAHA-epub) or patient-perceived sense of the care plan (PEC-epub). New analyses have shown that compared to eligible white participants, black participants more frequently did not enrol to the study. Enrolment of Black, indigenous, and people of colour benefited most form including and prioritizing practices most likely to care for them. We found no evidence of contamination (tool use, functional, or learned) between study arms. Conclusions: Use of an SDM tool improved some measures of SDM quality, without affecting treatment decisions and their sensibility, encounter duration, patient adherence, or clinical outcomes. Our results should calibrate expectations as to what could be accomplished by implementing SDM tools about anticoagulation in the care of patients with AF
Abstract 9816: Cholesterol Efflux Capacity Mediates The Relationship Between Neutrophils And Coronary Burden In Psoriasis
Authors: Alexander R Berg, Laurel Mendelsohn, Christin Hong, Ross O'Hagen, Maryia Svirydava, Haiou Li, Marcus Chen, Martin Playford, Nehal N Mehta, Heather L Teague
Journal: Circulation (2022)

Introduction: Psoriasis is a chronic inflammatory disease associated with increased levels of activated neutrophils, lower cholesterol efflux capacity (CEC), and subclinical atherosclerosis. High-density lipoprotein cholesterol efflux is the primary method of cholesterol removal from peripheral tissues and is linked to innate immunity and cardiovascular disease. Preclinical models suggest a strong relationship between CEC, neutrophil frequency and activation, and atherosclerosis, yet this relationship is understudied in clinical models. Hypothesis: (1) Psoriasis patients with high neutrophils have lower CEC and high non-calcified coronary burden (NCB); (2) CEC mediates the relationship between neutrophils and NCB. Methods: Coronary computed tomography angiography was used to quantitate NCB in one-hundred seventy-nine untreated psoriasis patients. Circulating neutrophils were measured via flow cytometry, and mean fluorescence intensity of CD62L and CD11b was determined. CEC was quantified using a cell-based ex-vivo assay measuring the ability of apolipoprotein B depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Results: Patients with high neutrophils had decreased CEC (0.93 (0.15) vs 1.00 (0.17); P =0.03) and higher NCB (1.24 (0.55) vs 1.10 (0.50); P =0.003). The relationship between neutrophils and NCB was mediated by CEC beyond adjustment for Framingham risk score, smoking status, and statin treatment (20%, P =&lt;0.001) ( Figure 1 ). CEC associated with neutrophil activation markers, CD11b and CD62L (β: -0.23 P =0.04, β:0.21, P =0.04). Finally, one year of biologic therapy improved CEC (0.08 (0.17) vs (-0.009 (0.19); P =0.008) and neutrophil counts (-0.45 (-1.36- -0.45) vs -0.14 (-0.60-0.42; P =0.004). Conclusion: Patients with more neutrophils had lower CEC and higher NCB. Further, CEC mediates the relationship between neutrophils and NCB, underscoring the relationship between neutrophils and CEC in atherosclerosis.
Abstract 9695: Characteristics, Treatment, and Mortality of Patients Hospitalized for ST-Elevation Myocardial Infarction Without Standard Modifiable Cardiovascular Risk Factors in China
Authors: Weihong Guo, Yunfeng Wang, AoXi Tian, Jiamin Liu, Haibo Zhang, Jing Li, Shengshou Hu, Xi Li, xin zheng
Journal: Circulation (2022)

Introduction: Previous studies found that a substantial proportion of ST-elevation myocardial infarction (STEMI) patients with no standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, smoking) at admission, had unexpected higher mortality compared with those with SMuRFs. However, little is known about what contributed to the excess risk of SMuRF-less patients. Methods: This study used a two-stage random sampling design to create a nationally representative sample of patients admitted with STEMI in China, from 2001 to 2015. We compared patient characteristics, treatments, and in-hospital mortality rates between SMuRF-less patients and those with SMuRFs, and established stepped mixed effect models on in-hospital mortality, to explore the potential contributors to different mortality risks (if exist). Results: Among 16541 patients included (aged 65±13 years, 30.0% women), 3288 (19.9%) were SMuRF-less. Compared with patients with SMuRFs, SMuRF-less patients were older (69 vs 65 years, p&lt;0.001), and presented with more severe clinical conditions (mini-Global Registry of Acute Coronary Events risk score; 151 vs 138, p&lt;0.001). SMuRF-less patients were less likely to receive primary percutaneous coronary intervention (17.3% vs 28.8%, p&lt;0.001), as well as dual antiplatelet therapy (59.4% vs 77.0%, p&lt;0.001), β-blocker (78.3% vs 85.7%, p&lt;0.001), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (49.9% vs 68.1%, p&lt;0.001), statin (69.9% vs 85.1%, p&lt;0.001). Meanwhile, SMuRF-less patients had higher in-hospital mortality (18.5% vs 10.5%, p&lt;0.001). Such difference was largely attenuated after adjusting for baseline characteristics (OR 1.45; 95%CI 1.29-1.64), while disappeared after additionally adjusting for in-hospital treatments (OR 1.04; 95%CI 0.91-1.19), particularly angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and statin. Conclusion: For the one-fifth patients with STEMI who had no SMuRFs the excess in-hospital mortality was associated with their relatively suboptimal treatments, highlighting the need for evidence-based therapy in SMuRF-less patients during hospitalization.
Abstract 9343: Predictive Value of Baseline Serum High-Sensitivity Troponin I and NT-proBNP for Cardiac Immunotoxicity Risk During Immune Checkpoint Inhibitor Therapy
Authors: Anjali Rao, Tanushree Prasad, Shayna Simon, Hong Zhu, Vishnu Venkatesh, Sadia Ali, Bonnie Bermas, Luigino Bernabela, Salman Bhai, James Brugarolas, Pedro Castillo, Alvin Chandra, Kathryn Dao, Pradeep P Mammen, Sonia Garg, Jade Homsi, Orhan Oz, Gregory Ratti, Chris Selby, Srilakshmi Vallabhaneni, Kathleen Zhang, James A De Lemos, John Sweetenham, Hans Hammers, Vlad G Zaha
Journal: Circulation (2022)

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, but rarely and unpredictably cause fulminant myocarditis. It is unknown if circulating cardiac biomarkers can predict immunotoxicity in a real-world patient population. Aim: To evaluate the predictive value of baseline levels of high-sensitivity troponin-I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) for myocardial injury (hs-TnI&gt;50ng/L) or potential heart failure (NT-proBNP&gt;300pg/mL) risk during ICI therapy. Methods: An institutional multidisciplinary working group developed a monitoring protocol for immune-related adverse events due to ICI. Data recorded during clinical treatment plans over 12 months starting 5/1/2021 were analyzed. Results: 621 patients received ICI therapy, and 6 developed myocarditis requiring hospitalization. Of 317 patients initiated on ICI after the start of this protocol, baseline and at least one follow-up hs-TnI and NT-proBNP values were measured in 183 and 126 patients, respectively. In 110 patients hs-TnI was undetectable (&lt;5ng/L) at baseline. In 66% of these patients hs-TnI remained undetectable on follow-up. Of 88 patients with baseline NT-proBNP below the diagnosis limit for heart failure (&lt;300 pg/mL), 75% had values below this limit on follow-up. The baseline value of the biomarkers was used as a predictor of increase in biomarkers during follow-up. Area under receiver operator curve for predicting an increase from baseline during ICI treatment was 0.67 for hs-TnI, 0.87 for NT-proBNP, and 0.86 combined (Figure). Conclusions: This single-center, prospectively protocolled, retrospectively-analyzed study indicates that hs-TnI and NT-proBNP values obtained at baseline and at least at one immunotherapy cycle can be used to categorize patients at risk or not for potential immunotoxicity during ICI treatment, thus may offer a helpful strategy in the monitoring and prevention of fulminant myocarditis.
Abstract 9729: Pulling Out All the Stops (for a Diagnosis): A Case of Progressive Dyspnea
Authors: John W Ostrominski, Monica L Hollowell, Deepak L Bhatt, Benjamin M Scirica
Journal: Circulation (2022)

A 63-year-old woman with hypertension, diabetes mellitus, severe obesity, obstructive sleep apnea, and history of GATA3+/ER+ breast cancer treated 14 years prior with neoadjuvant anthracycline-based chemotherapy and subsequent lumpectomy, chest radiotherapy, and letrozole presented to the emergency department with three weeks of progressive cough and exertional dyspnea. Physical examination revealed tachypnea, hypoxemia, a prominent P2, and jugular venous distension with a Kussmaul sign. Further investigation showed moderate hemolytic anemia, severe thrombocytopenia, and elevated natriuretic peptides. Electrocardiography revealed normal sinus rhythm, an S1Q3T3 pattern, and diffuse T wave inversions. Computed tomography angiography of the chest was notable for few small pulmonary nodules and diffuse vertebral osteosclerosis, consistent with osteoblastic metastases. Transthoracic echocardiography exhibited a moderately dilated RV with moderate systolic dysfunction, moderate TR, and an estimated RVSP of 79 mm Hg. Lung perfusion scintigraphy disclosed subtle subsegmental defects. Right heart catheterization (RHC) showed elevated right-sided filling pressures and severe precapillary pulmonary hypertension (RA 12 mm Hg, mPAP 51 mm Hg, PCWP 6 mm Hg, and PVR 775 dynes-sec/cm 5 ). There was no discernable shunt. These findings, coupled with the patient’s history, rapidly progressive symptoms, and hematologic derangements, raised suspicion for pulmonary tumor thrombotic microangiopathy (PTTM). A pulmonary capillary wedge blood aspirate was sent for cytology. Her clinical status rapidly worsened despite inhaled pulmonary vasodilators, hemodynamic support, and systemic glucocorticoids, precluding candidacy for empirical chemotherapy. She was transitioned to comfort measures only and suffered a bradycardic PEA arrest on hospital day 8. Autopsy was declined. Cytological analysis of the wedge blood aspirate ultimately revealed clusters of neoplastic GATA3+ cells, consistent with PTTM associated with late recurrence of breast carcinoma. This case highlights the rare instance of PTTM diagnosis aided by wedge cytology, reinforcing the multidimensional role of RHC in this extremely uncommon and devastating clinical entity.
Abstract 9808: Deletion of Arrdc4 Enhances Myocardial Glucose Transport and Ameliorates Ischemic Injury
Authors: Yoshinobu Nakayama, Aliya Masihuddin, Syed A Abdali, Jun Yoshioka
Journal: Circulation (2022)

Cardiomyocytes depend on glycolysis instead of oxidative phosphorylation during hypoxia and utilize glucose as a primary anaerobic energy source. Cardiac glucose transport is facilitated by the expression of glucose transporters (GLUT1 and GLUT4) on the cell surface. The arrestins are a family of proteins that regulate the signaling and trafficking of different receptors and transporters on the plasma membrane. As a scaffold protein, beta-arrestins mediate endocytosis and signal termination of beta-adrenergic receptors in cardiomyocytes. However, unlike the well-characterized beta-arrestins, the physiological roles of the related proteins termed alpha-arrestins remain largely unknown in the heart. In this study, we discovered for the first time that a member of alpha-arrestins, Arrestin Domain-Containing Protein 4 (Arrdc4), functions as a regulatory scaffold protein of GLUT1 and controls cardiac glucose metabolism. We found that Arrdc4 interacts with GLUT1 and promotes its endocytosis in cardiomyocytes. Interestingly, the cardiac expression of Arrdc4 is significantly upregulated by myocardial ischemia. Arrdc4 decreases cell surface expression of GLUT1 and suppresses glucose transport in the wild-type (WT) mouse heart. Then, we generated a novel Arrdc4 knockout (KO) mouse using CRISPR/Cas9 genome editing and characterized the effects of Arrdc4 in an animal model of myocardial infarction (MI) by coronary artery ligation in vivo. Surprisingly, Arrdc4-KO mice exhibit smaller infarct size, fewer apoptotic cells, and higher left ventricular (LV) fractional shortening, resulting in better post-MI survival than WT mice. Furthermore, using the Langendorff perfusion system, we found that Arrdc4-KO hearts augment cardiac glucose transport and preserve better LV mechanical function during anaerobic perfusion than WT hearts ex vivo. These results demonstrate that Arrdc4-KO cardiomyocytes coordinately maintain the optimal expression of GLUT1 on the cell surface, which leads to a metabolic rearrangement to secure energy homeostasis under oxygen- and nutrient-limited environments. In conclusion, we identified Arrdc4 as a new adaptor protein for GLUT1 in cardiomyocytes and a key player in cardiac metabolism in the ischemic heart.
Abstract 9410: Cardiovascular Disease Associated Metabolites TMA and TMAO Bind to Cystathionine Gamma-Lyase and Repress Its Enzymatic Production of Hydrogen Sulfide
Authors: Betemariam Sharew, Suzie Kim, Jacob Enders, Nazmin Bithi, Christopher Hine
Journal: Circulation (2022)

While the causative factors of smoking and hypertension leading to cardiovascular disease (CVD) are well understood, those involved with diet-induced CVD are not. One metabolite regulated by diet that is involved with cardio-protection and vasodilation is the gasotransmitter hydrogen sulfide (H 2 S). However, the molecular inhibition of H 2 S-generating enzymes via CVD-inducing diets is not fully understood, nor is it known if this is the causative event leading to CVD. Enzymatic H 2 S production in mammalian tissues and cells is primarily via the transsulfuration enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL). A high fat Western diet contributes to CVD through gut microbiome metabolic pathways and subsequent host enzymes converting choline and carnitine into the metabolites trimethylamine (TMA) and trimethylamine-N-oxide (TMAO). We hypothesized that TMA and TMAO lower H 2 S production by directly interacting with CGL to reduce enzymatic activity and that these gut-related metabolites’ inhibition account for some of the CVD risks. Results: Using a lead acetate assay, we discovered that these metabolites reduce enzymatic H 2 S production in a CGL-dependent manner from tissues ex vivo as well as from purified human CGL in vitro to a similar extent as propargylglycine (PAG), a known CGL suicide inhibitor that also happens to be a bacterial metabolite. We found that in vivo , hepatic and renal H 2 S production increased in antibiotic treated mice surface plasma resonance (SPR) and micro-scale thermophoresis (MST) assays revealed direct and specific physical interactions between TMA and TMAO with CGL. Additionally, pre-incubation with PAG blocked the binding of TMAO with CGL, indicating that the mechanism and location of inhibition are shared. Conclusion: Diet-induced gut metabolites TMA and TMAO bind CGL enzyme and suppress enzymatic production of cardioprotective H 2 S.
Abstract 9337: The Association of Echo Parameters With Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy. Insights From the Explorer-HCM Trial
Authors: Suzanne V Arnold, Kensey Gosch, Chantal Dolan, Jennifer T Fine, Ahmad Masri, Sara Saberi, Andrew Wang, Perry M Elliott, Sheila Hegde, Jenny Lam, Amy J Sehnert, Richard Bach, John A Spertus
Journal: Circulation (2022)

Introduction: The EXPLORER-HCM trial showed mavacamten, a direct cardiac myosin inhibitor, improved the health status of patients with obstructive hypertrophic cardiomyopathy (HCM). To explore physiologic mechanisms for this improvement, we examined cross-sectional and longitudinal associations of echocardiographic parameters with health status. Methods: EXPLORER-HCM was a 13-country, double-blind randomized trial of mavacamten or placebo for 30 weeks in symptomatic patients with obstructive HCM and peak LVOT gradient ≥50 mmHg. Health status was assessed with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS, range 0-100, higher=better). Using a series of multivariable linear regression models, we examined the association of 1) echo parameters with KCCQ-OS at baseline and 2) change in echo parameters with change in KCCQ-OS. Nonlinear associations were explored with cubic splines. As this was a mechanistic analysis, treatment was not included. Results: Among 196 patients (mean age 58±12 years, 39% women), mean KCCQ-OS was 67±18 at baseline and 76±19 at 30 weeks; mean change of 10±16 points. At baseline, only interventricular septal thickness (IVST) was significantly associated with KCCQ-OS in adjusted analyses (1.2-point decrease in KCCQ-OS per 1 mm higher IVST; 95% CI -2.2 to -0.2, p=0.015). However, when comparing changes in echo parameters with changes in KCCQ-os, decreases in LVOT gradient at rest, LVOT gradient post-exercise, LVOT gradient with Valsalva, LV mass, posterior wall thickness, and IVST were each associated with significant improvements in KCCQ-OS (FIGURE). Measures of diastolic function were not associated with KCCQ-OS, either cross-sectionally or longitudinally. Conclusions: Among patients with obstructive HCM, reductions in LVOT gradients, LV mass, and wall thickness (IVST&gt;posterior wall) were associated with significant improvements in patients’ symptoms, function, and quality of life.
Abstract 9569: Unplanned Readmission Rate in Tobacco Use Population After Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting: Propensity Matched Comparison
Authors: Kyeeun Park, Abi Watts, Pyi Phyo Aung, Nikhil Sikha
Journal: Circulation (2022)

Introduction: Tobacco use is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and associated with cardiac intervention complications. However, there is a lack of data on the effect of smoking status on the post cardiac procedural results. Methods: We conducted a retrospective analysis of the 2018 to 2019 Nationwide Readmission Database (NRD). Adult patients (Age &gt; 18) with tobacco use who underwent either PCI or CABG were selected using the ICD-10-CM diagnosis and procedure code. Discharge-level weight analysis was used to produce a national estimate. Propensity score matching (1:1) with age, sex, and comorbidity burden was performed and the outcomes were compared between matched cohorts. Results: During the study period, 1,392,730 patients underwent PCI (991,730; 71.2%) or CABG (401,000; 28.8%) of which 18,574 patients (1.3%) used tobacco. Patients who underwent PCI with tobacco use were younger (59.7 SE 0.1 vs 62.4 SE 0.2) and with more female population (25.7% vs 18.2%) compared to those who underwent CABG with tobacco use. In discharged patients with tobacco use, unplanned 30-day readmission rate was 9.0%. The majority of the readmission was due to ischemic heart diseases (89.4%) and 2.7% was due to complications of cardiac implants or grafts. A half of readmission occurred within 9 days after the discharge. 9,223 discharged patient with tobacco use who underwent PCI or CABG were propensity-matched. 30-day readmission rate was significantly lower in patients with PCI (8.5% vs 10.7%; p = 0.006). Furthermore, PCI was associated with shorter length of stay (3.5 days SE 0.1 vs 10.1 days SE 0.1; p &lt; 0.001) and lower total hospital cost ($111,492.2 SE 1,188 vs $231,603.6 SE 3,558.3; p &lt; 0.001). In-hospital mortality was similar in PCI and CABG groups (2.0% vs 1.8%, p = 0.26). Conclusions: 9.0% of tobacco use patients with ASCVD who underwent PCI or CABG had unplanned readmissions. The most common reason for readmission was ischemic heart disease, with more than 50% of patients returning to the hospital within the first two weeks of hospital discharge. Tobacco use patients who underwent PCI had statistically significantly lower readmission rates, length of stay, than their propensity-matched peers who underwent CABG.